The heart is a hollow, muscular organ that circulates blood throughout an organism's body by contracting rhythmically. In mammals, the heart has four-chambers situated such that the right atrium and ventricle are completely separated from the left atrium and ventricle. Normally, blood flows from systemic veins to the right atrium, and then to the right ventricle from which it is driven to the lungs via the pulmonary artery. Upon return from the lungs, the blood enters the left atrium, and then flows to the left ventricle from which it is driven into the systemic arteries.
Four main heart valves prevent the backflow of blood during the rhythmic contractions: the tricuspid, pulmonary, mitral, and aortic valves. The tricuspid valve separates the right atrium and right ventricle, the pulmonary valve separates the right atrium and pulmonary artery, the mitral valve separates the left atrium and left ventricle, and the aortic valve separates the left ventricle and aorta. Generally, patients having an abnormality of a heart valve are characterized as having valvular heart disease.
One way a heart valve can malfunction is by failing to open properly due to stenosis, requiring replacement of the valve by surgical or transcutaneous arterial means. Replacement valves are typically bioprosthetic valves made from valves of other animals, such as pig or cow. Unfortunately, over time, the replacement valves themselves are susceptible to problems such as stenosis, obstruction and calcification.
For years cardiac calcification was thought to be a passive degenerative phenomenon. Rajamannan's work in U.S. Pat. Appln. No. 2002/0159983 first attempted, unsuccessfully, to address the issue of stenosis and calcification of diseased heart valves. Rajamannan discloses a method for inhibiting stenosis, obstruction or calcification of heart valve tissue having live, non-fixed heart valve cells that contain an exogenous nucleic acid that encodes or activates endothelial nitric oxide synthase—a polypeptide having nitric oxide synthase activity. It was thought at the time that nitric oxide would stop the calcification of the live tissue before it was processed using glutaraldehyde. Rajamannan used a virus (e.g. retrovirus, adenovirus, or herpes virus) to introduce the exogenous nucleic acid (eNOS) by injection into a live cell of the heart valve (human or porcine—in vivo or in vitro) such that the polypeptide—endothelial nitric oxide synthase—is expressed. It was thought that the cell would make excessive amount of nitric oxide synthase that would stop calcification. Rajamannan also discloses administering an inhibitor of hydroxymethylglutaryl coA reductase activity, such as pravastatin, atorvastatin, simvastatin or lovastatin orally to the mammal and/or bathing the cells with bovine serum containing the foregoing. After the foregoing treatment, the human or porcine heart valve was fixed with glutaraldehyde. As noted above, this technique was unsuccessful.
What is needed are new methods and systems that inhibit the formation of stenosis, obstruction, and/or calcification of heart valves and bioprosthetic heart valves.